Lifitegrast is the generic name of compound of formula (I) (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)-propanoic acid.

Lifitegrast is a lymphocyte function-associated antigen 1 antagonist (LFA-1) that has been approved by the US Food and Drug Administration (FDA) in the form of ophthalmic solution for the treatment of signs and symptoms of dry eye disease.
Lifitegrast was first described in the patent family including WO2006/125119. However, this PCT application does not disclose any preparation process for this active compound. WO2009/139817 describes a process for the preparation of lifitegrast shown in scheme 1. This process includes obtaining intermediate 19 by reacting a benzyl-protected compound 12 with the acyl chloride of acid 18, and subsequently removing the benzyl group by Pd-catalyzed hydrogenation to give lifitegrast (1):

WO2011/050175 describes a process for the preparation of lifitegrast including obtaining intermediate 19 as described in WO2009/139817 and later removing the benzyl group by acid or basic hydrolysis.
Finally, WO2014/018748 describes a process for the preparation of lifitegrast including obtaining intermediate 19 as described in WO2009/139817 and later removing the benzyl group by phase transfer catalyst (biphasic conditions). WO2014/018748 also discloses the use of thionyl chloride (SOCl2) and N-Methylmorpholine (NMM) as alternative conditions for the preparation of the acyl chloride of 18.
Concerning the purification of lifitegrast, WO2009/139817 discloses a step of slurrying lifitegrast in methyl ethyl ketone (MEK) or acetonitrile to give lifitegrast Form A. In WO2011/050175 and WO2014/018748 it is specified that the crystallization from MEK is carried out with seed crystals of 99% purity and 99% ee. The optical purity reported for the resulting lifitegrast in these conditions is of 97.9%.
The preparation of lifitegrast according to the previous processes shows some drawbacks. In particular, toxic chlorinating reagents are used which is disadvantageous per se. In addition, these toxic substances and potentially genotoxic chlorinated impurities resulting from the use of these reagents must be removed from the final product until below the maximum limit permissible in the product for regulatory reasons, which signifies hard purifications. Further, attempts to reproduce the crystallization of lifitegrast in MEK of the prior art failed in the hands of the inventors when using a crude product with 98% purity. In fact, there is no disclosure in the prior art documents as to how to achieve the seed crystal used in the purification step having 99% purity and 99% ee.
Therefore, a need exists of providing alternative processes for the preparation of lifitegrast that are reproducible, easy to industrialize, and avoid the prior art problems.